DESCRIPTION (Adapted from the application): The immediate career goal of the candidate, Wendy S. Sprague, DVM, is to complete a mentored program investigating retrovirus immunoregulation and vaccine development culminating in the Ph.D. degree and additional postdoctoral research. Dr. Sprague's long-term goal is to become a principal investigator conducting research on immunomodulatory strategies against viral diseases of humans and animals. The research training program will be centered in the laboratory of sponsor Dr. Edward A. Hoover at Colorado State University. The environment has a strong record of extramural funding and scientist training. The candidate's training plan involves laboratory and didactic instruction in contemporary cellular and molecular research methods applied to an animal model of Acquired Immunodeficiency Syndrome (AIDS). The research proposed examines the mechanisms whereby dendritic cells (DC) may play a pivotal role in lentivirus infection and immunity by addressing four specific aims: (1) to culture and characterize feline blood-derived DC; (2) to determine whether DC pulsed with inactivated FIV can activate autologous T cells in vitro to elicit secondary antigen-specific CD4+ T helper cell and CD8+ cytotoxic T cell (CTL) responses in vitro; (3) to determine the ability of FIV-pulsed autologous DC to activate immune responses in vivo; and (4) to generate protective immunity via DC-targeted immunization. In Aim 1, feline DC will be cultured and characterized by phenotypic and functional criteria and compared with blood-derived DC of other species. In Aim 2, DC from KLH-immunized, FIV-vaccinated cats will be pulsed with inactivated virus and analyzed for the ability to induce antigen-specific T cell responses in vitro. In Aim 3 studies, the ability of autologous FIV-pulsed DC from FIV-naive cats to induce T cell and virus neutralizing antibody responses in vivo will be examined. Finally, in Aim 4 the capacity of FIV-DC-targeted immunization to protect cats from virulent viral infection will be assessed in vivo. Results of these DC-based vaccine studies will provide useful proof-of-principle information regarding the induction of protective immunity immunodeficiency virus infections.